Identification of Intracellular Phospholipases A<sub>2</sub>in the Human Eye: Involvement in Phagocytosis of Photoreceptor Outer Segments

Kolko, Miriam; Wang, Jinmei; Chen, Zhan; Poulsen, Kristian Arild; Prause, Jan Ulrik; Nissen, Mogens Holst; Heegaard, Steffen; Bazán, Nicolás G.

doi:10.1167/iovs.06-0865

Cited by 34 publications

(29 citation statements)

References 35 publications

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“…Remaining to be defined are the regulatory events triggered by POS phagocytosis, including signals that activate phospholipase A 2 , to cleave docosahexaenoic chains from phospholipids of the POS disk membranes. Several phospholipases A 2 are present in the RPE cells, and recently a low molecular weight phospholipase A 2 was suggested to be engaged in POS phagocytosis (34). Another question is how the release of DHA is coupled to NPD1 synthesis through a 15-lipoxygenase enzyme (26).…”

Section: Discussionmentioning

confidence: 99%

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Mukherjee

Marcheselli

Vaccari

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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100

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Photoreceptor cell (rods and cones) renewal is accompanied by intermittent shedding of the distal tips of the outer segment followed by their phagocytosis in the retinal pigment epithelial (RPE) cells. This renewal is essential for vision, and it is thought that it fosters survival of photoreceptors and of RPE cells. However, no specific survival messenger/mediators have as yet been identified. We show here that photoreceptor outer segment (POS) phagocytosis markedly attenuates oxidative stress-induced apoptosis in ARPE-19 cells in culture. This phenomenon does not seem to be a generalized outcome of phagocytosis because nonbiological (polystyrene microsphere) phagocytosis did not elicit protection. The free docosahexaenoic acid (DHA) pool size and neuroprotectin D1 (NPD1) content increased during POS phagocytosis but not during microspheres phagocytosis. We have also explored other lipid mediators [lipoxin A4 and 15(S)-and 12(S)-hydroxyeicosatetraenoic acids] under these conditions and found them unchanged upon POS phagocytosis. Moreover, oxidative stress challenge to RPE cells undergoing POS phagocytosis further increased DHA and NPD1 content. Under these conditions, NPD1 was found within the RPE cells as well as in the culture medium, suggesting autocrine and paracrine bioactivity. Furthermore, using deuterium-labeled DHA, we show that as the availability of free DHA increases during oxidative stress, NPD1 synthesis is augmented in ARPE-19 cells. Our data suggest a distinct signaling that promotes survival of photoreceptor and RPE cells by enhancing the synthesis of NPD1 during phagocytosis. Taken together, NPD1 may be a mediator that promotes homeostatic regulation of cell integrity during photoreceptor cell renewal. docosahexaenoic acid ͉ polystyrene microspheres ͉ retinal pigment epithelial cells ͉ survival ͉ omega-3 fatty acids

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Section: Discussionmentioning

confidence: 99%

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Mukherjee

Marcheselli

Vaccari

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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100

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“…Photoreceptors shed outer segment tips, which are then phagocytized by RPE cells in a daily, intermittent, and circadian fashion in mammals (19). The length of the outer segments remains constant as a consequence of the well-regulated biogenesis of outer segment membrane components in inner segments, coupled to the phagocytosis of the shed tips at an equal compensatory rate.…”

Section: Dha Supply and Retention In The Cnsmentioning

confidence: 99%

Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease

Bazán

2009

Journal of Lipid Research

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Docosahexaenoic acid (DHA), the main omega-3 fatty acid, is concentrated and avidly retained in membrane phospholipids of the nervous system. DHA is involved in brain and retina function, aging, and neurological and psychiatric/ behavioral illnesses. Neuroprotectin D1 (NPD1), the firstidentified stereoselective bioactive product of DHA, exerts neuroprotection in models of experimental stroke by downregulating brain ischemia reperfusion (BIR)-induced leukocyte infiltration, proinflammatory signaling, and infarct size. Moreover, NPD1 inhibits cytokine-mediated cyclooxygenase-2

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“…Experiments in which the isolated purifed subunits of Gt were added to Gt-poor ROS membranes in the presence or absence of light demonstrated that Gt ␤ ␥ subunits stimulate PLA2 activity ( 101 ). Furthermore, it has been recently reported that calcium-independent PLA2 group VIA may play an important role in the regulation of retinal pigment epithelium phagocytosis of photoreceptor OSs and that it may also be involved in the regulation of photoreceptor cell renewal ( 104 ).…”

Section: Plcmentioning

confidence: 99%

Lipid second messengers and related enzymes in vertebrate rod outer segments

Giusto

Pasquaré

Salvador

et al. 2010

Journal of Lipid Research

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outer segment of the cell is comprised of a stack of many hundreds of densely packed discs, each of which represents a double layer of infolded plasma membrane. It has been suggested that phospholipid moieties in these membranes are metabolically active and are closely involved in the generation of physiological mediators. Modifi cations in the metabolism of photoreceptor membrane glycerolipids have been linked to the transduction of visual stimuli ( 3 ). Rod outer segment (ROS) membranes are composed of 50% protein and 50% lipid, by weight ( 2 ). Phospholipids and cholesterol represent nearly 90-95% and 4-6% (w/w) of total lipids, respectively. Rhodopsin accounts for at least 80-85% (w/w) of the total proteins ( 4-6 ) in disc ROS membranes. The rest are mainly proteins involved in phototransduction. The composition of mammalian ROS membrane phospholipids indicates that the major phospholipids are phosphatidylethanolamine (PE) and phosphatidylcholine (PC), along with relatively large amounts of phosphatidylserine (PS) (15%). Small amounts (less than 1% each) of sphingomyelin, phosphatidylinositol (PI) and phosphatidic acid (PA) are found in these membranes ( 7-13 ). In vertebrates, cholesterol (exclusively as the free sterol) is the principal neutral lipid, comprising The vertebrate photoreceptor cell is composed of different cellular compartments [outer segment (OS), inner segment (IS), and synaptic terminal (ST)], all of which differ in their lipid and protein content ( 1, 2 ). The photoreceptor is a highly specialized cell that responds to light stimulus and transmits this response to adjoining neurons for ultimate relay to the visual centers of the brain. TheThis work was supported

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Identification of Intracellular Phospholipases A₂in the Human Eye: Involvement in Phagocytosis of Photoreceptor Outer Segments

Abstract: Various intracellular PLA(2) subtypes are present in the human retina. iPLA(2)-VIA may play an important role in the regulation of RPE phagocytosis of POS and may also be involved in the regulation of photoreceptor cell renewal.

Cited by 34 publications

References 35 publications

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease

Lipid second messengers and related enzymes in vertebrate rod outer segments

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Identification of Intracellular Phospholipases A2in the Human Eye: Involvement in Phagocytosis of Photoreceptor Outer Segments

Abstract: Various intracellular PLA(2) subtypes are present in the human retina. iPLA(2)-VIA may play an important role in the regulation of RPE phagocytosis of POS and may also be involved in the regulation of photoreceptor cell renewal.

Cited by 34 publications

References 35 publications

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Photoreceptor outer segment phagocytosis attenuates oxidative stress-induced apoptosis with concomitant neuroprotectin D1 synthesis

Neuroprotectin D1-mediated anti-inflammatory and survival signaling in stroke, retinal degenerations, and Alzheimer's disease

Lipid second messengers and related enzymes in vertebrate rod outer segments

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Identification of Intracellular Phospholipases A₂in the Human Eye: Involvement in Phagocytosis of Photoreceptor Outer Segments